title: Prognostic significance of the CD10+CD19+CD34+ B-progenitor immunophenotype in children with acute lymphoblastic leukemia: a report from the Children's Cancer Group.
abstract: Leukemic cells from most patients with B-lineage acute lymphoblastic leukemia (ALL) appear to originate from normal B-lymphocyte precursors. The earliest B-cell progenitors coexpress the antigens CD10, CD19, or CD34 on their cell surfaces. In a large cohort of 2028 children with ALL, we compared treatment outcomes of a subset of B-lineage ALL patients with CD10+CD19+CD34+ immature B-progenitor leukemia (BPL) to the treatment outcomes of the remaining CD19+ B-lineage ALL patients. Pediatric B-lineage ALL cases enrolled on risk-adjusted ALL treatment protocols of the Children's Cancer Group were immunophenotypically classified as BPL or non-BPL. Patients were stratified further into age groups of > or = 1 year and <12 months. Event-free survival (EFS) outcomes were calculated by standard life table methods. BPL patients in both age groups generally had more favorable presenting characteristics than non-BPL controls. Within the age group of > or = 1 year, BPL patients had a slightly better EFS outcome than non-BPL patients, with 3-year estimates of 83.9% (SD = 1.1%) vs. 78.8% (SD = 1.8%), respectively (P = 0.10). Infants with BPL, representing one-fifth of the total infant patient population, had a significantly better EFS outcome than infants with non-BPL (three-year EFS: 82.4%, SD = 9.2% vs. 34.4%, SD = 5.9%, P = 0.006). In univariate analyses, the relative hazard rate (RHR) was 3.73 for non-BPL vs BPL and this marked difference in EFS outcome was maintained at 5 years of follow-up. The favorable prognostic influence of the BPL immunophenotype for infants remained significant in multivariate analyses with an RHR of 2.72 for non-BPL vs BPL (P = 0.05). CD10+CD19+CD34+ immature B-progenitor immunophenotype is associated with favorable characteristics for children with ALL and identifies a subset of infants who achieve favorable EFS outcomes.
authors.affiliation: Children's Cancer Group ALL Biology Reference Laboratory, and Biotherapy Institute, University of Minnesota Academic Health Center, Roseville, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
authors.forename: H
authors.initials: H
authors.lastname: Sather
authors.forename: P
authors.initials: P
authors.lastname: Gaynon
authors.forename: D
authors.initials: D
authors.lastname: Arthur
authors.forename: J
authors.initials: J
authors.lastname: Nachman
authors.forename: M
authors.initials: M
authors.lastname: Sensel
authors.forename: P
authors.initials: P
authors.lastname: Steinherz
authors.forename: R
authors.initials: R
authors.lastname: Hutchinson
authors.forename: M
authors.initials: M
authors.lastname: Trigg
authors.forename: G
authors.initials: G
authors.lastname: Reaman
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D018941:Antigens, CD19 / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015260:Neprilysin / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D015260:Neprilysin